Polycystic Ovarian Syndrome (PCOS), also referred to as hyperandrogenic anovulation (HA), or Stein–Leventhal syndrome is a symptom complex of multifactorial and polygenic pathology characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features.
M/C endocrine disorder of women of reproductive age
M/C pathological cause for hirsutism in women
M/C cause of rapid-onset hirsutism: Testosterone producing tumour
M/C cause of anovulatory infertility
Multi- factorial and polygenic aetiology:
Aetiology of PCOS appears to be ‘multi- factorial and polygenic’. Both nature and nurture seem to play a role in contributing to PCOS. It has been found to cluster in families, particular in those with history of polycystic ovaries (PCO), non-insulin dependent diabetes mellitus, cardiovascular disease (CVD) and breast cancer. Meanwhile, excessive intake of excitatory amino acids that can affect the pituitary regulation of the ovary cycles such as monosodium glutamate (MSG), exposure to endocrine-disrupting chemicals such as pesticides, and sedentary lifestyle are also believed to result in PCOS.
Lack of exercise
Family history of PCOS
M/C gene mutation: Cyp 21 gene
These usually result in exaggerated phenotypes of PCOS
HAIR-AN syndrome (hyperandrogenism, insulin resistance and acanthosis nigricans)
Metabolic X syndrome
Androgen excess: Central event in the pathogenesis of PCOS
PCOS is characterized by hypothalamic–pituitary–ovary axis dysfunction and anovulation but, unlike other causes of ovulatory failure that feature insufficient ovarian follicle growth or suppressed gonadotropin secretion (or both), PCOS typically includes androgen excess and subtle alterations (not detected by routine tests) in serum levels of gonadotropins and estrogens. PCOS is characterized by increased levels of circulating androgen, polycystic ovarian morphology (PCOM), arrested follicle development, and anovulatory infertility.
The syndrome is also associated with persistently rapid gonadotropin-releasing hormone pulses, an excess of luteinizing hormone, and insufficient follicle-stimulating hormone (FSH) secretion, which contribute to excessive ovarian androgen production and ovulatory dysfunction.
↑ Gonadotropins → ↑ GnRH pulse frequency → ↑ LH/FSH ratio (2:1) → ↑ Androgens
Insulin resistance, and compensatory hyperinsulinemia enhances ovarian (and adrenal) androgen production and increases androgen bioavailability through reduced levels of sex hormone–binding globulin.
90%–95% of anovulatory women presenting to infertility clinics have PCOS
Dysmenorrhoea (increased estrone)
Oligo/amenorrhea cycles: ≤ 8/year (90% cases)
Associated metabolic morbidities:
PCOS is associated with high rates of glucose intolerance resulting from defects in insulin action and β-cell function. Obesity substantially exacerbates these defects so obese reproductive-age women with PCOS are at very high rates of glucose intolerance.
DM-2 (10% cases)
Obesity (low adiponectin levels)
Short term complications:
Irregular menstrual cycles
Endometrial carcinoma (↑ estrone)
PCOS is a diagnosis of exclusion, based primarily on the presence of hyperandrogenism, ovulatory dysfunction and PCOM.
Diagnostic criteria for PCOS have been offered by 3 groups. Each issuing group considers PCOS a diagnosis of exclusion, and other diagnoses, such as congenital adrenal hyperplasia, nonclassic adrenal hyperplasia, Cushing syndrome, androgen-secreting tumor, idiopathic hyperandrogenism, idiopathic hirsutism, hyperprolactinemia, and thyroid disorders must be excluded.
National Institutes of Health/National Institute of Child Health and Human Disease (NIH/NICHD) | 1992
European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) “Rotterdam criteria” | 2004
Androgen Excess and PCOS Society | 2006
At Least 2 criterias required
Rotterdam criteria divided the disease into four phenotypes:
Frank/classic polycystic ovary PCOS (chronic anovulation, hyperandrogenism, and polycystic ovaries)
Classic non-polycystic ovary PCOS (chronic anovulation, hyperandrogenism, and normal ovaries)
Non-classic ovulatory PCOS (regular menstrual cycles, hyperandrogenism, and polycystic ovaries)
Non-classic mild or normoandrogenic PCOS (chronic anovulation, normal androgens, and polycystic ovaries)
Modified Ferriman-Gallway index:
9 sites examined for hirsutism. Score of ≥ 8 diagnostic (maximum score 36)
2-h glucose challenge test:
Considering the baseline defects in insulin sensitivity and secretion in PCOS and the deleterious impact of obesity on these measures, women with this condition are expected to have a high prevalence of impaired glucose tolerance (IGT), defined by a 2h post-challenge glucose level 140–200 mg/dl and type 2 diabetes.
Transvaginal sonography (TVS):
Multiple (≥ 12) cysts measuring 2-9mm
“Chain of pearl” or “ring of pearls” appearance in ovaries
Treatment should be tailored to the complaints and needs of the patient and involves targeting metabolic abnormalities through lifestyle changes, medication and potentially surgery for the prevention and management of excess weight, androgen suppression and/or blockade, endometrial protection, reproductive therapy and the detection and treatment of psychological features.
Menstrual disturbances: OCPs
Obesity: Lifestyle modifications
Insulin resistance: Metformin
Hirsutism/acne: OCP + cyproterone acetate
Infertility: Clomiphene citrate
Indicated in failed medical therapy, ovarian hyperstimulation, infertility or previous pregnancy losses. Surgery restores endocrine milieu and improves fertility for a year or so. After a year, pelvic adhesions may reduce the fertility.
Laparoscopic drilling of ≤ 4 cysts in each ovary by laser/unipolar electrocautery